Decrease in cold tolerance of aged rats caused by the enhanced endogenous adenosine activity.
During severe cold exposure, old rats (24-28 months) were less capable of maintaining their body temperature compared to young rats (3-6 months) due to lower rate of heat production. Single injection of adenosine deaminase (AD) (converts adenosine to inosine) significantly increased thermogenesis in both young and old rats. However, doubling the dose of AD was required for optimal thermogenic response in old rats. In contrast, the similar enhancements in both thermogenesis and cold tolerance were observed in both young and old rats receiving the same optimal doses of specific adenosine receptor antagonists. These results lead to the suggestion that the lower capability of aged rats to withstand cold exposure could be due to an increase in adenosine stimulation because of the decreased endogenous AD activity rather than an increase in adenosine receptor sensitivity. This notion is further supported by the finding that the AD activity in the neck muscle, a key site for shivering thermogenesis, was significantly lower in old rats as compared to their younger counterparts before and after cold exposure.